Review Articles in 2020

The prevalence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is projected to continue to increase worldwide. In this Review, Huang, El-Serag and Loomba discuss the global epidemiology and risk factors for NAFLD-related HCC, and propose strategies to tackle this problem.

Human microphysiology systems (MPS) have evolved as experimental model systems. This Review explores these so-called organ-on-a-chip systems and the role of biomimetic human liver MPS in drug development and precision medicine, providing insights into their design and use as models of liver physiology and disease.

The common end stage of liver disease is decompensated cirrhosis and the further development towards acute-on-chronic liver failure. In this Review, the authors discuss the possible pathogenic, diagnostic and therapeutic role of the gut microbiota in decompensation of cirrhosis and progression to acute-on-chronic liver failure.

A gluten-free diet is currently the only effective treatment for coeliac disease but an increased understanding of disease pathogenesis has led to the identification of several potential therapeutic targets. This Review provides a broad overview of current and emerging therapies for coeliac disease.

Dietary fibre has been shown to be beneficial for gastrointestinal health. This Review discusses the physicochemical and functional characteristics of dietary fibres and provides insight into their role in gastrointestinal health and the management of gastrointestinal disorders.

Chronic liver injury leads to liver inflammation and fibrosis, through which activated myofibroblasts in the liver secrete extracellular matrix proteins that generate the fibrous scar. This Review summarizes studies of the molecular mechanisms underlying liver fibrosis and its reversibility.

This Review describes the pathophysiological roles of peroxisome proliferator-activated receptors (PPARs) in nonalcoholic steatohepatitis and related metabolic diseases, and summarizes the preclinical and clinical data on the use of PPAR agonists to treat nonalcoholic steatohepatitis as part of a systemic metabolic disease.

Emerging data have revealed that nonalcoholic steatohepatitis (NASH) and fibrosis are associated with the reactivation of developmental pathways in the liver injury response. This Review describes the role of these pathways in liver development and in the pathogenesis of NASH and fibrosis.

The management of viral hepatitis in the setting of pregnancy requires special consideration. This Review examines each hepatitis virus individually to address the effect of pregnancy on the natural history of infection and how the viral infections influence maternal and infant outcomes, including mother-to-child transmission.

Transcriptional regulatory mechanisms have a dual role in specifying intestinal epithelial identity and enabling microbial responsiveness. In this Review, Rawls and colleagues describe what is currently known about the epigenetic patterning and transcription factors responsible for this duality.

Inflammatory bowel disease (IBD) has different manifestations and associated risk factors between the sexes. This Review explores the sex-based differences in presentation and management of IBD, as well as insights into sex-based differences in pathogenesis and underlying mechanisms inferred from basic research.

Food addiction is an eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift towards hedonic mechanisms. This Review summarizes the physiology of food addiction in obesity as it relates to BGM interactions and provides insights into treatment targets for food addiction aimed at each level of the BGM axis.

The liver has a broad range of regenerative capacities. In this Review, Michalopoulos and Bhushan describe the regenerative mechanisms employed by hepatic cells after liver injury as well as the experimental models used to investigate these mechanisms and discuss the clinical implications.

In this Review, Thomson et al. describe the immunobiology underlying liver graft tolerance and failure, and discuss therapeutic approaches for minimization or withdrawal of anti-rejection immunosuppressive drug therapy post transplantation.

Gastrointestinal dysfunction (including dysphagia and constipation) can occur in Parkinson disease (PD), with evidence that they can arise prior to diagnosis of PD. This Review describes new insights into the mechanisms and pathophysiology of the gastrointestinal involvement of PD, including clinical manifestations.

Intestinal epithelial glycosylation is influenced by host genetics, the environment and the gut microbiota. In this Review, Kudelka et al. describe the functions of epithelial glycans and discuss the role of epithelial glycosylation in Crohn’s disease and ulcerative colitis.

Modern therapies for malignant liver tumours integrate neoadjuvant and adjuvant strategies. This broad Review discusses these approaches, including advances in staged surgeries, systemic therapies, ablation therapies and liver transplantation.

Evidence points to a crucial role of necroptosis and pyroptosis as important modes of programmed cell death in the intestine in addition to apoptosis. This Review discusses advances in our understanding of apoptosis, necroptosis and pyroptosis as major cell death pathways that can result in pathophysiological outcomes.

Single-cell transcriptomic technologies are transforming our understanding of cellular diversity and function in health and disease. This Review discusses how these technologies have been applied in hepatology, advancing our understanding of cellular heterogeneity and providing novel insights into liver biology such as metabolic zonation and the mechanisms underpinning liver regeneration.

Hepatitis B virus (HBV) infection remains a global public health issue. This Review provides insights into the evolution of HBV and discusses the mechanisms by which HBV and hepatitis delta virus diversity occurs and the influence of this diversity on disease progression and treatment response.